This is an application for support for a SCOR in Osteoarthritis at Rush- Presbyterian-St. Luke's Medical Center in Chicago. It represents a continuation and an extension of the current SCOR grant (2-P50-AR-39239) with closely related projects within an integrated program entitled "Osteoarthritis: A continuum (From Cartilage Metabolism to Early Detection and Treatment)." The overall theme of the projects outlined in this application will continue to be the tissue following injury and how do articular cartilage, with major emphasis on the potential of cartilage cells to repair the tissue following injury and how articular chondrocytes existing as individual satellite metabolic centers control the integrity of the extracellular matrix. The process of chondrocytic chondrolysis and the blocking of tissue repair either by mediators or by fragments of extracellular matrix components is a segment of these investigations. Comparative studies of tissues from human knee and ankle joints should reveal differences in composition and metabolism that predispose the knee joint to and/or protect the ankle joint from progressive degeneration. Though our unique collaboration with the Regional Organ Bank of Illinois, we have available a very large number of tissues from "normal" donors. We plan to establish the sequence of physiological and biochemical events which, in the case of knee articular cartilage, my progress to OA, but in ankle cartilage may be non-progressive due to intrinsic factors of to the ability of this tissue to repair itself. This important approach is of significant clinical relevance. The clinical research project will evaluate and quantify in a longitudinal study the relationship between dynamic loading, cartilage metabolism and the progression of medical compartment knee OA in collaboration with an ongoing NIH sponsored Multi- Purpose Arthritis and Musculoskeletal Center at Northwestern University of Chicago. All these studies combine their efforts to look at OA as a disease of the organ, the diarthrodial joint, and its specific tissue, the articular cartilage. The proposed studies will encompass four individual, overlapping and integrated projects supplemented by three Core Facilities. Although this represents a renewal application, some of the aims of the programs/projects have been changed to reflect the incorporation of new areas of emphasis into consolidated projects and an incorporation of specific goals as outlined in the Future Directions of the 1994-95 NIH sponsored OA Workshop.